Charge Conversional Biomimetic Nanosystem for Synergistic Photodynamic/Protein Therapy.

Cytochrome C (Cytc) has received considerable attention due to its ability to induce tumor apoptosis and generate oxygen to improve photodynamic therapy (PDT) efficiency. However, the damage to normal tissues caused by nonspecific accumulation of Cytc limits its application. Herein, in order to reduce its toxicity to normal tissues while retaining its activity, a charge conversional biomimetic nanosystem (CA/Ce6@MSN-4T1) is proposed to improve the tumor targeting ability and realize controlled release of Cytc in the tumor microenvironment. This nanosystem is constructed by coating tumor cell membrane on mesoporous silica nanoparticles coloaded with a photosensitizer (chlorin e6, Ce6) and the citraconic anhydride conjugated Cytc (CA) for synergistic photodynamic/protein therapy. The coating of the tumor cell membrane endows the nanoparticles with homologous targeting ability to the same cancer cells as well as immune escaping capability. CA undergoes charge conversion in the acidic environment of the tumor to achieve a controlled release of Cytc. The released Cytc can relieve cellular hypoxia to improve the PDT efficiency of Ce6 and can induce programmed cell death. Both in vitro and in vivo studies demonstrated that CA/Ce6@MSN-4T1 can efficiently inhibit the growth of tumors through synergistic photodynamic/protein therapy, and meanwhile show reduced side effects on normal tissues.

Biomimetic Nanocomposites Camouflaged with Hybrid Cell Membranes for Accurate Therapy of Early-Stage Glioma.

Glioma features high fatality rate and short survival time of patients due to its fast growth speed and high invasiveness, hence timely treatment of early-stage glioma is extremely important. However, the blood brain barrier (BBB) severely prevents therapeutic agents from entering the brain; meanwhile, the non-targeted distribution of agents always causes side effects to vulnerable cerebral tissues. Therefore, delivery systems that possess both BBB penetrability and precise glioma targeting ability are keenly desired. We herein proposed a hybrid cell membrane (HM) camouflage strategy to construct therapeutic nanocomposites, in which HM consisting of brain metastatic breast cancer cell membrane and glioma cell membrane was prepared with a simple membrane fusion pathway. By coating HM onto drug-loaded nanoparticles, the as-obtained biomimetic therapeutic agent (termed HMGINPs) inherited satisfying BBB penetrability and homologous glioma targeting ability simultaneously from the two source cells. HMGINPs exhibited good biocompatibility and superior therapeutic efficacy towards early-stage glioma.

Monitoring Subtle Changes of Blood-Brain Barrier Permeability via Detection of MiRNA-155 in Brain Microvasculature.

The changes of blood-brain barrier (BBB) permeability need to be sensitively reported when purposefully regulating the BBB or during some brain diseases. Currently available techniques for assessment of BBB integrity all suffer from limited sensitivity and only report serious BBB damage. Here, a targeted activatable nanoprobe is created to monitor subtle changes of BBB permeability by detecting the expression levels of BBB permeability-related miRNA (miRNA-155) in brain microvessel endothelial cells (BMECs). The probe is fabricated by coating the BMEC membrane on calcium phosphate (CaP)-mineralized metal-organic framework (MOF) nanoparticles loaded with hybridization chain reaction (HCR) probes. The coating of the BMEC membrane endows the nanoprobe with homologous targeting ability to BBB, and HCR probes released and escaped from lysosomes can be specifically lightened by miRNA-155. The activatable nanoprobe is able to monitor BBB permeability in inflammatory and AD mice. This work provides a new idea for highly sensitive evaluation of the BBB permeability, which has guiding significance in regulating BBB and formulating targeted therapeutic strategies.